Phytol exerts sedative-like effects and modulates the diazepam and flumazenil's action, possibly through the GABA A receptor interaction pathway.

Autor: Islam MT; Pharmacy Discipline, Khulna University, Khulna 9208, Bangladesh; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Dhaka, Bangladesh. Electronic address: dmt.islam@bsmrstu.edu.bd., Ferdous J; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Dhaka, Bangladesh; Department of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Microbial Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh., Hasan MSA; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Dhaka, Bangladesh., Hashem A; Microbial Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh., Bappi MH; School of Pharmacy, Jeonbuk National University, Jeonju 54896, Republic of Korea., Ansari SA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O Box 2457, Riyadh 11451, Saudi Arabia., Islam MA; Pharmacy Discipline, Khulna University, Khulna 9208, Bangladesh; Department of Pharmacy, East West University, Dhaka 1212, Bangladesh., Saifuzzaman M; Pharmacy Discipline, Khulna University, Khulna 9208, Bangladesh.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2024 Nov 01; Vol. 842, pp. 138007. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1016/j.neulet.2024.138007
Abstrakt: This study aimed at the evaluation of the sedative effect of phytol (PHY) with possible molecular mechanisms through in vivo and in silico studies. For this, adult male mice were randomly divided into six individual groups, namely control (vehicle), two standards (DZP: diazepam at 2 m/kg, FLU: flumazenil at 0.1 mg/kg), three test groups (PHY at 25, 50, and 75 mg/kg), and three combined groups with the DZP-2 and/or FLU-0.1 with PHY-75 mg/kg. After thirty minutes, each animal was treated with thiopental sodium (TS) at 40 mg/kg to produce sedation and observed for latency and duration of sleep up to 4 h. In silico studies were performed with the 6X3X protein of the GABA A receptor α1 and β2 subunits. The results demonstrate that PHY dose-dependently enhanced sleep duration in animals. However, it produced an insignificant sleep duration compared to the control and standard groups. It also significantly (p < 0.05) decreased the latency and increased the duration of sleep with DZP-2, while reducing these parameters with FLU-0.1. In in silico studies, DZP and FLU exhibited binding affinities with 6X3X by -6.8 and -6.9 kcal/mol, respectively, while PHY exhibited -6.9 kcal/mol. Taken together, PHY may exert a sedative-like effect in TS-induced sleeping mice and modulate the effects of DZP and FLU, possibly through interacting with the 6X3X protein of the GABA A receptor. PHY may be one of the good candidates for the management of sleep disturbances, such as insomnia.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE